AB0455 DRUGS, AUTOANTIBODIES AND GENES CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC DAMAGE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: G. Olivieri, F. Ceccarelli, C. Pirone, L. Picciariello, F. Natalucci, C. Ciccacci, C. Perricone, F. R. Spinelli, C. Alessandri, P. Borgiani, F. Conti
Journal: Annals of the Rheumatic Diseases (2022)

Background Genetic contribution to development of chronic damage have been scarcely investigated in systemic lupus erythematosus (SLE). In fact, whereas most studies have looked for an association between genetic variants and SLE susceptibility or disease phenotypes, only few have focused on the relationship between these biomarkers and damage development. Objectives Moving from these premises, we firstly analyzed the distribution of organ damage in a cohort of SLE patients and secondly we evaluate the role of clinical and genetic factors in determining the development of chronic damage. Methods Caucasian SLE patients, diagnosed according with 1997 ACR criteria, were enrolled, and clinical and laboratory data were collected. Based on literature data, we selected a panel of 17 SNPs of following genes STAT4, IL10, IRAK1, HCP5, MIR146a, ATG16L1, IRGM, ATG5, MIR124, MIR1279, TNFSF4, CD40. Genotyping was performed by allelic discrimination assays. A phenotype-genotype correlation analysis was performed by evaluating specific domains of SLICC Damage Index (SDI). Results Among 175 Caucasian SLE patients, 105 (60%) exhibited damage (SDI ≥1) with a median value of 1.0 (IQR 3.0). The musculoskeletal (26.2%), neuropsychiatric (24.6%) and ocular domains (20.6%) were involved most frequently. The presence of damage was associated with higher age, longer disease duration, neuropsychiatric (NP) manifestations, anti-phospholipid syndrome and the positivity of anti-dsDNA antibodies. Concerning therapies cyclophosphamide, mycophenolate mofetil and glucocorticoids resulted associated with the development of damage. The genotype/phenotype correlation analysis showed an association between renal damage, identified in 6.9% of patients, and rs2205960 of TNFSF4 (p=0.001; OR 17.0). This SNP resulted significantly associated with end-stage renal disease (p= 0.018, OR 9.68) and estimated GFR&lt;50% (p=0.025, OR 1.06, Figure 1). The rs1463335 of MIR1279 gene was associated with the development of NP damage (p=0.029; OR 2.783). The multivariate logistic regression analysis confirmed the associations between TNFSF4 rs2205960 SNP and renal damage (p=0.020, r=2.53) and between NP damage and rs1463335 of MIR1279 gene (p=0.013, r=1.26)]. Figure 1. Association between renal damage and rs2205960 of TNFSF4 (p=0.001). In addition, this SNP resulted significantly associated with the development of two specific items of SDI renal domain: estimated glomerular filtration rate (GFR) &lt;50% and end-stage renal disease (ESRD) (p=0.025, p=0.018 respectively). Conclusion We showed the role of age, drugs, and autoantibody profile in determining chronic damage. Our data suggest a possible role of genetic background in determining the development of renal and neuropsychiatric damage, as demonstrated by the association with polymorphisms of TFNSF4 and MIR1279, respectively. These results agree with previous studies suggesting the involvement of TNFSF4 in Lupus nephritis and microRNA in neuroinflammation. Disclosure of Interests None declared